EP0784992B1 - Treatment device for malignant changes of tissue - Google Patents
Treatment device for malignant changes of tissue Download PDFInfo
- Publication number
- EP0784992B1 EP0784992B1 EP97100159A EP97100159A EP0784992B1 EP 0784992 B1 EP0784992 B1 EP 0784992B1 EP 97100159 A EP97100159 A EP 97100159A EP 97100159 A EP97100159 A EP 97100159A EP 0784992 B1 EP0784992 B1 EP 0784992B1
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- European Patent Office
- Prior art keywords
- sensor
- actuator head
- drug
- sensor actuator
- supporting
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/40—Applying electric fields by inductive or capacitive coupling ; Applying radio-frequency signals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N2/00—Magnetotherapy
- A61N2/002—Magnetotherapy in combination with another treatment
Definitions
- the invention relates to a device for treating living cell tissue, the device comprising a sensor-actuator head with a pH sensor and a drug delivery device with a has an active ingredient storage container, and wherein the pH sensor and the drug delivery device for drug dosage depending on the pH measurement to a control device are connected.
- WO-A-9408655 which is used to form the preamble of claim 1, a transdermally acting drug delivery device in metered form with a sensor actuator head is known. This removes liquid from the skin, analyzes this liquid and uses the analysis result to control the supply of active substance.
- the active ingredient When the active ingredient is administered transdermally, it is transported via the bloodstream to a treatment area. In addition to a delayed feedback of the effect, the active ingredient also reaches the body via the bloodstream, where it can cause undesirable side effects.
- chemotherapeutic agents which are intended to damage the pathogenic parts of the organ, but preferably not the rest of the organism.
- systemic and regional dosing of chemotherapeutic agents is problematic, since on the one hand a corresponding active ingredient concentration is aimed at being highly effective compared to, for example, a tumor, but on the other hand there is a risk of damage to healthy tissue through unspecific intake.
- US Patent 4,003,379 describes a so-called "drug delivery system” with which medication can be administered within the body of a patient.
- the device can be implanted in the body.
- radioactive active substances can be monitored with this device and active substance can be dosed depending on the concentration of the radioactivity.
- the concentration of radioactivity cannot be used to draw conclusions about the effect of the medication on the treated tissue area.
- the object of the present invention is to provide a device create with which target-oriented chemotherapy is possible, in which the stress and damage to the unaffected areas of the body is at least largely reduced.
- the sensor actuator head at least with the pH sensor and the drug delivery device is designed so that it is inside the body in tumorous tissue area can be used and this treatment area contacted directly in the application position with a support and contact surface that the pH sensor for Determination of the acidification of the immediate environment of this tumorous Tissue area is arranged, and that the active ingredient is one for lifting the pH value of the immediate vicinity of the tumorous tissue area and / or to reduce the acidification of the tumor cells themselves.
- the pH sensor is used to monitor the treatment area the acidification in the treatment area can be determined.
- Changes in the pH value allow conclusions to be drawn about the metabolic activities of the tumor cells, so that appropriate treatment adjustments can be made. This is based on the finding that tumor growth and spread must be viewed as a process of cellular self-organization which, apart from changes in the cellular signal processing apparatus, is essentially controlled by the microenvironment of the tumor.
- the pH of the tumor's microenvironment plays a key role in this. If, for example, a pH setpoint of 7.4 is specified, the control device, based on the measurement of the existing pH value as the actual value, regulates the dosage of the medicinal active ingredient until the setpoint, in the example pH 7.4, is reached.
- the medicinal active substance can be an active substance for neutralizing the pH gradient.
- an active substance for blocking the proton pump on the cell membranes of the tumor cells or an active substance for blocking the molecular biological agents (for example antisense products)
- an active substance for blocking the proton pump on the cell membranes of the tumor cells
- an active substance for blocking the molecular biological agents for example antisense products
- the medicinal active ingredient is applied directly to a tumor to be treated and, at the same time, continuous monitoring takes place there in the immediate vicinity of the treatment site with the aid of the pH sensor and, if appropriate, further sensors.
- the metering will be adapted by the control device in accordance with the setpoint values.
- An independently operating control loop is thus formed, by means of which the dosage of the active substance to be applied can be continuously updated.
- electrodes for physical influencing of the tumorous tissue area by electrical and / or electromagnetic fields by means of iontophoresis for raising the measured pH value in the immediate vicinity of a tumorous tissue area can be provided on the sensor actuator head be provided.
- a direct voltage or an alternating voltage can be applied to the electrodes.
- the field is changed as a function of the respective pH measured value, so that a control loop and thus a targeted treatment with "feedback" is also available in this regard.
- the pH sensor can be semiconductor-based on the basis of a conductivity and impedance measurement, in the case of a semiconductor-based pH sensor preferably at least one ion-selective field effect transistor (IS-FET) is provided for the latter.
- IS-FET ion-selective field effect transistor
- At least one further sensor in particular an ion or molecular sensor, is provided in addition to at least one pH sensor.
- additional sensors in addition to changes in pH, additional, therapy-relevant changes in the microenvironment of a tumor can be recorded, and appropriate measures when applying the medicinal active substance can be derived from these additional measurement data.
- the active substance delivery device expediently has at least one porous membrane and an active substance supply to this membrane, a metering device being located in the active substance supply and being connected to a metering control.
- a metering device being located in the active substance supply and being connected to a metering control.
- the sensor or sensors as well as the porous membrane form the support and contact surface for the tissue area to be treated. With this support and contact surface for the tissue area to be treated, at least two electrodes for iontophoretic purposes can also be provided, which are connected to a voltage source via electrical lines.
- the sensor / actuator head forms a complete functional unit and that in particular it has at least one active substance storage container, one or more metering device (s) connected to the porous membrane or the like with metering control and at least one pH sensor ,
- the functional unit has at least one pH sensor, at least two electrodes for iontophoretic purposes, a voltage source and a control device.
- a device according to the invention is used as a complete, functional unit within the body and can remain there for a planned treatment period. Since all components necessary for the function are available, a connection to the outside is not necessary.
- the active substance storage container preferably together with the dosing device and the dosing control, is arranged remote from the sensor actuator head and that one or more connecting lines between these functional groups for the dosed supply of the active substance to the sensor actuator head and for connection to the electrodes.
- the sensor actuator head itself can be made particularly small in this embodiment, so that it can also be used in difficult to access places within the body.
- the supply unit which is set apart from the sensor actuator head, is arranged so that it is easily accessible, so that refilling with a medicinal active substance, possibly an external power supply and the like, can be implemented easily.
- a device 1 shown in FIG. 1 is used to apply medicinal active substance in the area of living cell tissue.
- it can be a tumor 2 to be treated, which is indicated in FIG. 1.
- the device 1 has a sensor actuator head 3, a supply unit 4 which is set apart from this sensor actuator head 3 in the exemplary embodiment according to FIG. 1, and a connecting line 5 between the sensor actuator head 3 and supply unit 4.
- an active substance storage container 6 preferably with a metering device (not shown here) as well as a metering control 7 and a power supply 8.
- the sensor actuator head 3 has on its support and contact surface 13 a porous membrane 9 (cf. also FIG. 2), an active ingredient supply to this membrane 9 and sensors 10 adjacent to the membrane.
- the membrane 9 and the sensors 10 contact the treatment area in the application position.
- the medical agent can be supplied from the reservoir 6 to the porous membrane 9 within the connecting line 5, which in the practical exemplary embodiment can be formed by a catheter tube, and in addition, electrical connections between the sensor (s) 10 and the metering control 7 are accommodated in the connecting line 5 , This can be clearly seen in the cross-sectional illustration according to FIG. 3.
- the connecting tube for the active substance is 11 and the electrical lines 12.
- active medical substance can be applied directly to the area to be treated, for example a tumor 2.
- the sensor actuator head 3 is placed directly on the area to be treated and the medical agent can then be supplied in this area via the porous membrane 9.
- the treatment area can be checked with the aid of the sensors 10 and, based on the measurement results, the dosage of the active substance can be exactly adjusted via the metering control 7 connected to the sensors 10.
- At least one of the sensors 10 is a pH sensor, since for successful immunotherapy, for example, monitoring the pH of the microenvironment of the area to be treated and also influencing this environment by varying the pH, in particular by corresponding addition of active substance, is essential Meaning is.
- chemotherapeutic concepts also rely on the steep, extracellular pH gradients to be broken down.
- a plurality of pH sensors can also be provided within the application area, it being possible for two or more pH sensors to be arranged at a distance from one another for an extracellular gradient measurement.
- Ion-selective field effect transistors are preferably used as the pH sensor.
- further sensors 10 in particular ion or molecular sensors, can be provided in order to obtain even more meaningful measurement results of the microenvironment of the area to be treated. A very targeted, effective treatment is then possible.
- Figures 4 and 5 show a modified embodiment of a device 1a, in which the sensor-actuator head 3a forms a complete functional unit.
- This sensor actuator head 3 a also contains all assemblies which are accommodated in the supply unit 4 in the exemplary embodiment according to FIG. 1.
- a compact unit results which can remain within the body as a self-sufficient unit for a corresponding treatment period.
- FIG. 5 still shows in the area of the support and contact surface 13, within which the porous membrane 9 and the sensor or sensors 10 are located, in the corner areas or adhesive regions 14 arranged on the edge.
- the sensor actuator head can 3a or the sensor actuator head 3 according to FIGS. 1 and 2 are pressed onto the area to be treated and is then held by adhesive adhesion.
- the adhesive regions 14 can also be used for iontophoretic purposes and are then designed to be electrically conductive and connected to a voltage source via connecting lines.
- a replaceable or rechargeable battery 8 (FIG. 1) can be provided as the power supply for the metering control and the like, or there is also the possibility that a thermoelectric power supply or a galvanic power supply formed with the aid of the body fluid is provided. Thermoelectric or galvanic power supplies are particularly advantageous in connection with the embodiment of the device according to the invention shown in FIGS. 4 and 5.
- FIG. 6 shows yet another embodiment variant of a sensor / actuator head 3b, which is essentially tubular and has a strip-shaped, longitudinally oriented support and contact surface on its outer surface.
- This embodiment is used in particular for treatment within hollow organs. It should be mentioned here that several support and contact surfaces can also be provided distributed around the circumference of the tubular sensor actuator head.
- the other embodiments of application heads can also be equipped with a plurality of support and contact surfaces and within them porous membranes 9 and sensors 10.
- a connection 15 for an external active substance container in particular for refilling the active substance, is also indicated.
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Description
Die Erfindung bezieht sich auf eine Vorrichtung zum Behandeln von lebendem Zellgewebe, wobei die Vorrichtung einen Sensor-Aktuatorkopf mit einem pH-Sensor und einer Wirkstoffabgabeeinrichtung mit einem einen Wirkstoff bevorratenden Behälter aufweist, und wobei der pH-Sensor und die Wirkstoffabgabeeinrichtung zur Wirkstoffdosierung in Abhängigkeit der pH-Wertmessung an eine Steuereinrichtung angeschlossenen sind.The invention relates to a device for treating living cell tissue, the device comprising a sensor-actuator head with a pH sensor and a drug delivery device with a has an active ingredient storage container, and wherein the pH sensor and the drug delivery device for drug dosage depending on the pH measurement to a control device are connected.
Aus der WO-A-9408655, die zur Bildung des Oberbegriffs des Anspruchs 1 herangezogen werden ist, ist eine transdermal wirkende Verabreichungsvorrichtung
für Medikamente in dosierter Form mit einem Sensor-Aktuatorkopf
bekannt. Damit wird der Haut Flüssigkeit entzogen,
diese Flüssigkeit analysiert und das Analyseergebnis zur Steuerung
der Wirkstoffzufuhr herangezogen.
Bei der transdermalen Verabreichung des Wirkstoffes wird dieser
über den Blutkreislauf zu einem Behandlungsbereich transportiert.
Neben einer verzögerten Wirkungsrückmeldung gelangt dabei der
Wirkstoff über den Blutkreislauf jedoch auch an Stellen des Körpers,
wo er unerwünschte Nebenwirkungen hervorrufen kann.From WO-A-9408655, which is used to form the preamble of claim 1, a transdermally acting drug delivery device in metered form with a sensor actuator head is known. This removes liquid from the skin, analyzes this liquid and uses the analysis result to control the supply of active substance.
When the active ingredient is administered transdermally, it is transported via the bloodstream to a treatment area. In addition to a delayed feedback of the effect, the active ingredient also reaches the body via the bloodstream, where it can cause undesirable side effects.
Bei der Krebstherapie ist es bereits bekannt, Chemotherapeutika
einzusetzen, die die pathogenen Organteile, möglichst aber nicht
den übrigen Organismus schädigen sollen.
Die systemische und regionale Dosierung der Chemotherapeutika ist
jedoch problematisch, da einerseits durch eine entsprechende
Wirkstoffkonzentration eine hohe Wirksamkeit gegenüber zum Beispiel
einem Tumor angestrebt wird, andererseits jedoch durch unspezifische
Aufnahme aber dann die Gefahr der Schädigung des gesunden Gewebes
besteht.In cancer therapy, it is already known to use chemotherapeutic agents which are intended to damage the pathogenic parts of the organ, but preferably not the rest of the organism.
However, the systemic and regional dosing of chemotherapeutic agents is problematic, since on the one hand a corresponding active ingredient concentration is aimed at being highly effective compared to, for example, a tumor, but on the other hand there is a risk of damage to healthy tissue through unspecific intake.
Das US-Patent 4 003 379 beschreibt ein sogenanntes "Drug Delivery
System", mit dem Medikamente innerhalb des Körpers eines Patienten
verabreicht werden können. Die Vorrichtung ist dazu in den Körper
implantierbar.
Zur Krebsbehandlung können mit dieser Vorrichtung radioaktive
Wirkstoffe überwacht und in Abhängigkeit der Konzentration der
Radioaktivität Wirkstoff dosiert verabreicht werden.
Auch hierbei kann aus der Konzentration der Radioaktivität nicht
auf die Wirkung des Medikamentes auf den behandelten Gewebebereich
rückgeschlossen werden.US Patent 4,003,379 describes a so-called "drug delivery system" with which medication can be administered within the body of a patient. For this purpose, the device can be implanted in the body.
For cancer treatment, radioactive active substances can be monitored with this device and active substance can be dosed depending on the concentration of the radioactivity.
Here, too, the concentration of radioactivity cannot be used to draw conclusions about the effect of the medication on the treated tissue area.
Aufgabe der vorliegenden Erfindung ist es, eine Vorrichtung zu schaffen, mit der eine targetorientierte Chemotherapie möglich ist, bei der die Belastung und Schädigung der nicht betroffenen Bereiche des Körpers zumindest weitgehend reduziert ist.The object of the present invention is to provide a device create with which target-oriented chemotherapy is possible, in which the stress and damage to the unaffected areas of the body is at least largely reduced.
Zur Lösung dieser Aufgabe wird vorgeschlagen, daß der Sensor-Aktuatorkopf zumindest mit dem pH-Sensor und der Wirkstoffabgabeeinrichtung derart ausgebildet ist, daß er innerhalb des Körpers im tumorösen Gewebebereich einsetzbar ist und diesen Behandlungsbereich in Applikationsstellung mit einer Auflage- und Kontaktfläche direkt kontaktiert, daß der pH-Sensor zur Bestimmung der Ansäuerung der unmittelbaren Umgebung dieses tumorösen Gewebebereichs angeordnet ist, und daß der Wirkstoff ein solcher zur Anhebung des pH-Wertes der unmittelbaren Umgebung des tumorösen Gewebebereichs und/oder zur Reduzierung der Ansäuerung der Tumorzellen selbst ist.To solve this problem it is proposed that the sensor actuator head at least with the pH sensor and the drug delivery device is designed so that it is inside the body in tumorous tissue area can be used and this treatment area contacted directly in the application position with a support and contact surface that the pH sensor for Determination of the acidification of the immediate environment of this tumorous Tissue area is arranged, and that the active ingredient is one for lifting the pH value of the immediate vicinity of the tumorous tissue area and / or to reduce the acidification of the tumor cells themselves.
Zur Überwachung des Behandlungsbereiches dient der pH-Sensor, durch den die Ansäuerung im Behandlungsbereich bestimmt werden kann. The pH sensor is used to monitor the treatment area the acidification in the treatment area can be determined.
Änderungen des pH-Wertes lassen Rückschlüsse auf die metabolischen
Aktivitäten der Tumor-Zellen zu, so daß dadurch entsprechende
Behandlungsanpassungen vorgenommen werden können. Dem liegt die
Erkenntnis zugrunde, daß Wachstum und Ausbreitung von Tumoren als
ein Prozeß zellulärer Selbst-Organisation betrachtet werden müssen,
der, abgesehen von Veränderungen im zellulären Signal-Verarbeitungs-Apparat,
wesentlich von der Mikro-Umgebung des Tumors gesteuert
wird. Dabei spielt der pH-Wert der Mikroumgebung des Tumors eine
zentrale Schlüsselrolle.
Wird beispielsweise ein pH-Sollwert von 7,4 vorgegeben, so erfolgt
durch die Steuereinrichtung aufgrund der Messung des vorhandenen
pH-Wertes als Istwert, eine geregelte Dosierung des medizinischen
Wirkstoffes, bis der Sollwert, im Beispiel pH 7,4, erreicht ist.
Der medizinische Wirkstoff kann ein Wirkstoff zur Neutralisation
des pH-Gradienten sein. Weiterhin kommt ein Wirkstoff (Antagonist)
zur Blockade der Protonenpumpe an den Zellmembranen der Tumorzellen
oder ein Wirkstoff zur Blockade der molekularbiologischen Agentien
(beispielsweise Antisens-Produkte) in Betracht.
Zur chemischen Beeinflussung wird der medizinische Wirkstoff
unmittelbar bei einem zu behandelnden Tumor appliziert und
gleichzeitig erfolgt dort auch in unmittelbarer Umgebung des
Behandlungsortes mit Hilfe des pH-Sensors und gegebenenfalls weiterer
Sensoren während der Behandlung eine laufende Überwachung. Aufgrund
der Meßwerte wird die Dosierung entsprechend den Sollwertvorgaben
von der Steuereinrichtung angepaßt werden. Es ist somit ein
selbständig arbeitender Regelkreis gebildet, durch den eine laufende
Dosierungsnachführung mit dem zu applizierten Wirkstoff vorgenommen
werden kann.Changes in the pH value allow conclusions to be drawn about the metabolic activities of the tumor cells, so that appropriate treatment adjustments can be made. This is based on the finding that tumor growth and spread must be viewed as a process of cellular self-organization which, apart from changes in the cellular signal processing apparatus, is essentially controlled by the microenvironment of the tumor. The pH of the tumor's microenvironment plays a key role in this.
If, for example, a pH setpoint of 7.4 is specified, the control device, based on the measurement of the existing pH value as the actual value, regulates the dosage of the medicinal active ingredient until the setpoint, in the example pH 7.4, is reached. The medicinal active substance can be an active substance for neutralizing the pH gradient. Furthermore, an active substance (antagonist) for blocking the proton pump on the cell membranes of the tumor cells or an active substance for blocking the molecular biological agents (for example antisense products) can be considered.
For chemical influencing, the medicinal active ingredient is applied directly to a tumor to be treated and, at the same time, continuous monitoring takes place there in the immediate vicinity of the treatment site with the aid of the pH sensor and, if appropriate, further sensors. On the basis of the measured values, the metering will be adapted by the control device in accordance with the setpoint values. An independently operating control loop is thus formed, by means of which the dosage of the active substance to be applied can be continuously updated.
In Kombination mit der chemischen Beeinflussung des
tumorösen Gewebes, können nach einer Ausgestaltung der Erfindung
am Sensor-Aktuatorkopf Elektroden zur
physikalischen Beeinflussung des tumorösen Gewebebereiches durch
elektrische und/oder elektromagnetische Felder mittels Iontophorese
zur Anhebung des gemessenen pH-Wertes in der unmittelbaren Umgebung
eines tumorösen Gewebebereichs vorgesehen sein.
An die Elektroden kann eine Gleichspannung oder eine Wechselspannung
angelegt werden. Auch hierbei wird die Änderung des Feldes in
Abhängigkeit von dem jeweiligen pH-Meßwert vorgenommen, so daß auch
diesbezüglich ein Regelkreis und somit eine gezielte Behandlung
mit "Feedback"vorhanden ist.In combination with the chemical influencing of the tumorous tissue, according to an embodiment of the invention, electrodes for physical influencing of the tumorous tissue area by electrical and / or electromagnetic fields by means of iontophoresis for raising the measured pH value in the immediate vicinity of a tumorous tissue area can be provided on the sensor actuator head be provided.
A direct voltage or an alternating voltage can be applied to the electrodes. Here too, the field is changed as a function of the respective pH measured value, so that a control loop and thus a targeted treatment with "feedback" is also available in this regard.
Der pH-Sensor kann auf Halbleiterbasis auf der Basis einer
Leitfähigkeits- und Impedanzmessung ausgebildet sein, wobei bei
einem pH-Sensor auf Halbleiterbasis für diesen vorzugsweise
wenigstens ein ionenselektiver Feldeffekttransistor (IS-FET)
vorgesehen ist.
Mit einem pH-Sensor auf Halbleiterbasis ist eine hohe Meßgenauigkeit
erzielbar und ein Sensor auf der Basis einer Leitfähigkeits- und
Impedanzmessung läßt sich in bestimmten Anwendungen (Leber, Magen)
einfacher anwenden.The pH sensor can be semiconductor-based on the basis of a conductivity and impedance measurement, in the case of a semiconductor-based pH sensor preferably at least one ion-selective field effect transistor (IS-FET) is provided for the latter.
With a pH sensor based on semiconductors a high measuring accuracy can be achieved and a sensor based on a conductivity and impedance measurement is easier to use in certain applications (liver, stomach).
Gegebenenfalls ist zusätzlich zu wenigstens einem pH-Sensor
wenigstens ein weiterer Sensor, insbesondere ein Ionen- oder
Molekularsensor vorgesehen.
Mit diesen zusätzlichen Sensoren lassen sich außer pH-Wertänderungen
auch noch zusätzliche, therapierelevante Änderungen in der
Mikroumgebung eines Tumors erfassen und aus diesen zusätzlichen
Meßdaten können entsprechende Maßnahmen beim Applizieren des
medizinischen Wirkstoffes abgeleitet werden. If necessary, at least one further sensor, in particular an ion or molecular sensor, is provided in addition to at least one pH sensor.
With these additional sensors, in addition to changes in pH, additional, therapy-relevant changes in the microenvironment of a tumor can be recorded, and appropriate measures when applying the medicinal active substance can be derived from these additional measurement data.
Zweckmäßigerweise weist die Wirkstoffabgabeeinrichtung vorzugsweise
wenigstens eine poröse Membran und eine Wirkstoff-Zuführung zu
dieser Membrane auf, wobei sich bei der Wirkstoff-Zuführung eine
Dosiereinrichtung befindet, die an eine Dosiersteuerung angeschlossen
ist.
Damit ist eine regional begrenzte und dosierte Zuführung von
Wirkstoff möglich.
Dabei bilden der oder die Sensoren sowie die gegebenenfalls
vorgesehene, poröse Membrane die Auflage- und Kontaktfläche für
den zu behandelnden Gewebebereich.
Bei dieser Auflage- und Kontaktfläche für den zu behandelnden
Gewebebereich können auch wenigstens zwei Elektroden zu iontophoretischen
Zwecken vorgesehen sind, die über elektrische Leitungen
mit einer Spannungsquelle verbunden sind.The active substance delivery device expediently has at least one porous membrane and an active substance supply to this membrane, a metering device being located in the active substance supply and being connected to a metering control.
This enables a regionally limited and dosed supply of active ingredient.
The sensor or sensors as well as the porous membrane, if provided, form the support and contact surface for the tissue area to be treated.
With this support and contact surface for the tissue area to be treated, at least two electrodes for iontophoretic purposes can also be provided, which are connected to a voltage source via electrical lines.
Eine Ausführungsform der Erfindung sieht vor, daß der Sensor-Aktuatorkopf
eine komplette Funktionseinheit bildet und daß diese
insbesondere wenigstens einen Wirkstoff-Vorratsbehälter, eine oder
mehrere, mit der porösen Membrane oder dergleichen verbundene
Dosiereinrichtung(en) mit Dosiersteuerung sowie zumindest einen
pH-Sensor aufweist.
Zusätzlich besteht für eine physikalische Beeinflussung auch
die Möglichkeit, daß die Funktionseinheit wenigstens einen pH-Sensor,
wenigstens zwei Elektroden zu iontophoretischen Zwecken,
eine Spannungsquelle sowie eine Steuereinrichtung aufweist.
Eine erfindungsgemäße Vorrichtung wird als komplette, funktionstüchtige
Einheit innerhalb des Körpers eingesetzt und kann dort über
einen vorgesehenen Behandlungszeitraum verbleiben. Da alle zur
Funktion notwendigen Komponenten vorhanden sind, ist eine
Verbindung nach außen nicht erforderlich. One embodiment of the invention provides that the sensor / actuator head forms a complete functional unit and that in particular it has at least one active substance storage container, one or more metering device (s) connected to the porous membrane or the like with metering control and at least one pH sensor ,
In addition, for physical influencing there is also the possibility that the functional unit has at least one pH sensor, at least two electrodes for iontophoretic purposes, a voltage source and a control device.
A device according to the invention is used as a complete, functional unit within the body and can remain there for a planned treatment period. Since all components necessary for the function are available, a connection to the outside is not necessary.
Es besteht aber nach einer anderen Ausführungsform der Erfindung
auch die Möglichkeit, daß der Wirkstoff-Vorratsbehälter,
vorzugsweise zusammen mit der Dosiereinrichtung und der Dosiersteuerung,
von dem Sensor-Aktuatorkopf abgesetzt angeordnet ist
und daß eine oder mehrere Verbindungsleitungen zwischen diesen
Funktionsgruppen zum dosierten Zuführen des
Wirkstoffes zu dem Sensor-Aktuatorkopf und zum Verbinden mit
den Elektroden vorgesehen ist.
Der Sensor-Aktuatorkopf selbst kann bei dieser Ausführungsform
besonders klein ausgebildet sein, so daß er auch an schwierig
zugänglichen Stellen innerhalb des Körpers einsetzbar ist. Außerdem
besteht hierbei die Möglichkeit, daß die zum Sensor-Aktuatorkopf
abgesetzte Versorgungseinheit gut zugänglich angeordnet wird, so
daß ein Nachfüllen mit medizinischem Wirkstoff, eine eventuell
externe Stromzuführung und dergleichen, einfach realisierbar sind.However, according to another embodiment of the invention, there is also the possibility that the active substance storage container, preferably together with the dosing device and the dosing control, is arranged remote from the sensor actuator head and that one or more connecting lines between these functional groups for the dosed supply of the active substance to the sensor actuator head and for connection to the electrodes.
The sensor actuator head itself can be made particularly small in this embodiment, so that it can also be used in difficult to access places within the body. In addition, there is the possibility that the supply unit, which is set apart from the sensor actuator head, is arranged so that it is easily accessible, so that refilling with a medicinal active substance, possibly an external power supply and the like, can be implemented easily.
Vorzugsweise sind bei der Auflage- und Kontaktfläche des Sensor-Aktuatorkopfes,
insbesondere randseitig, Haftregionen zum
vorzugsweise adhäsiven Anhaften des Sensor-Aktuatorkopfes an dem
zu behandelnden Gewebebereich vorgesehen.
Dadurch kann der Sensor-Aktuatorkopf durch einfaches Ansetzen und
Andrücken an dem zu behandelnden Bereich befestigt werden und
zusätzliche Befestigungsmaßnahmen sind dadurch entbehrlich.
Vorteilhaft ist es dabei, wenn die Haftregionen des Sensor-Aktuatorskopfes
elektrisch leitend ausgebildet sind und gleichzeitig
als Elektroden für die Iontophorese dienen.
Dies ist platzsparend und vereinfacht den Aufbau des Sensor-Aktuatorkopfes.
Zusätzliche Ausgestaltungen der Erfindung sind in den weiteren
Unteransprüchen aufgeführt.
Nachstehend ist die Erfindung mit ihren wesentlichen Einzelheiten
anhand der Zeichnungen noch näher erläutert.
Es zeigt:
- Figur 1
- eine etwas schematisierte Darstellung einer erfindungsgemäßen Vorrichtung mit einem Sensor-Aktuatorkopf sowie einer dazu abgesetzt angeordneten und über eine Verbindungsleitung verbundenen Versorgungseinheit,
Figur 2- eine Unterseitenansicht des in Figur 1 gezeigten Sensor-Aktuatorkopfes,
Figur 3- eine Schnittdarstellung der Verbindungsleitung zwischen Sensor-Aktuatorkopf und Versorgungseinheit gemäß Figur 1,
Figur 4- eine andere Ausführungsform der erfindungsgemäßen Vorrichtung in perspektivischer Darstellung,
Figur 5- eine Unterseitenansicht der in
Figur 4 gezeigten Vorrichtung, und Figur 6- eine röhrenförmige Ausbildung eines Sensor-Aktuatorkopfes mit Blick auf die Kontaktfläche für den Einsatz in Hohlorganen.
As a result, the sensor / actuator head can be attached to the area to be treated by simply attaching and pressing it on, and additional attachment measures are therefore unnecessary.
It is advantageous if the adhesive regions of the sensor-actuator head are designed to be electrically conductive and at the same time serve as electrodes for iontophoresis.
This is space-saving and simplifies the construction of the sensor actuator head.
Additional embodiments of the invention are listed in the further subclaims.
The invention with its essential details is explained in more detail below with reference to the drawings.
It shows:
- Figure 1
- 1 shows a somewhat schematic representation of a device according to the invention with a sensor actuator head and a supply unit arranged at a distance from it and connected via a connecting line,
- Figure 2
- 2 shows a bottom view of the sensor actuator head shown in FIG. 1,
- Figure 3
- 2 shows a sectional view of the connecting line between the sensor actuator head and the supply unit according to FIG. 1,
- Figure 4
- another embodiment of the device according to the invention in perspective view,
- Figure 5
- a bottom view of the device shown in Figure 4, and
- Figure 6
- a tubular design of a sensor actuator head with a view of the contact surface for use in hollow organs.
Eine in Figur 1 gezeigte Vorrichtung 1 dient zum Applizieren von
medizinischem Wirkstoff im Bereich von lebendem Zellgewebe. Es
kann sich dabei insbesondere um einen zu behandelnden Tumor 2
handeln, der in Figur 1 angedeutet ist.
Die Vorrichtung 1 weist einen Sensor-Aktuatorkopf 3, eine im
Ausführungsbeispiel gemäß Figur 1 zu diesem Sensor-Aktuatorkopf
3 abgesetzte Versorgungseinheit 4 sowie eine Verbindungsleitung
5 zwischen Sensor-Aktuatorkopf 3 und Versorgungseinheit 4 auf.
Innerhalb der Versorgungseinheit 4 befindet sich ein Wirkstoff-Vorratsbehälter
6 vorzugsweise mit einer hier nicht näher
dargestellten Dosiereinrichtung sowie einer Dosiersteuerung 7 und
eine Stromversorgung 8.
Der Sensor-Aktuatorkopf 3 weist an seiner Auflage- und Kontaktfläche
13 eine poröse Membrane 9 (vgl. auch Figur 2), eine
Wirkstoff-Zuführung zu dieser Membrane 9 sowie benachbart zu der
Membrane Sensoren 10 auf. Die Membrane 9 sowie die Sensoren 10
kontaktieren in Applikationsstellung den Behandlungsbereich.
Innerhalb der Verbindungsleitung 5, die im praktischen Ausführungsbeispiel
durch einen Katheterschlauch gebildet sein kann, kann
der medizinische Wirkstoff vom Vorratsbehälter 6 der porösen
Membrane 9 zugeführt werden und außerdem sind in der Verbindungsleitung
5 auch elektrische Verbindungen zwischen dem oder den
Sensoren 10 und der Dosiersteuerung 7 untergebracht. Dies ist
in der Querschnittdarstellung gemäß Figur 3 gut erkennbar. Der
Verbindungsschlauch für den Wirkstoff ist hierbei mit 11 und die
elektrischen Leitungen sind mit 12 bezeichnet.A device 1 shown in FIG. 1 is used to apply medicinal active substance in the area of living cell tissue. In particular, it can be a
The device 1 has a
The
Mit Hilfe der erfindungsgemäßen Vorrichtung kann medizinischer
Wirkstoff direkt bei dem zu behandelnden Bereich, beispielsweise
einem Tumor 2 appliziert werden. Dazu wird der Sensor-Aktuatorkopf
3 direkt auf den zu behandelnden Bereich aufgesetzt und über die
poröse Membrane 9 kann dann in diesem Bereich der medizinische
Wirkstoff zugeführt werden. Mit Hilfe der Sensoren 10 kann eine
Kontrolle des Behandlungsbereiches erfolgen und aufgrund der
Meßergebnisse kann über die mit den Sensoren 10 verbundene
Dosiersteuerung 7 eine exakte Anpassung der Wirkstoffdosierung
vorgenommen werden.
Zumindest einer der Sensoren 10 ist dabei ein pH-Sensor, da für
eine erfolgreiche Immuntherapie beispielsweise die Überwachung
des PH-Wertes der Mikroumgebung des zu behandelnden Bereiches
und auch eine Beeinflussung dieser Umgebung durch Variation des
pH-Wertes, insbesondere durch entsprechende Wirkstoffzugabe, von
wesentlicher Bedeutung ist. Auch andere chemotherapeutische
Konzepte sind darauf angewiesen, daß die steilen, extrazellulären
pH-Gradienten abgebaut werden.
Es können auch innerhalb des Applikationsbereiches mehrere pH-Sensoren
vorgesehen sein, wobei zwei oder mehrere pH-Sensoren
für eine extrazelluläre Gradientenmessung zueinander beabstandet
angeordnet sein können. With the aid of the device according to the invention, active medical substance can be applied directly to the area to be treated, for example a
At least one of the
A plurality of pH sensors can also be provided within the application area, it being possible for two or more pH sensors to be arranged at a distance from one another for an extracellular gradient measurement.
Als pH-Sensor werden vorzugsweise ionenselektive Feldeffekttransistoren
(IS-FET) eingesetzt.
Außerdem können noch weitere Sensoren 10, insbesondere Ionen- oder
Molekularsensoren vorgesehen sein, um noch aussagekräftigere
Meßergebnisse der Mikroumgebung des zu behandelnden Bereiches zu
erhalten. Damit ist dann eine sehr gezielte, wirksame Behandlung
möglich.
Die Figuren 4 und 5 zeigen eine abgewandelte Ausführungsform einer
Vorrichtung 1a, bei der der Sensor-Aktuatorkopf 3a eine komplette
Funktionseinheit bildet. Dieser Sensor-Aktuatorkopf 3a beinhaltet
auch alle Baugruppen, die bei dem Ausführungsbeispiel gemäß Figur
1 in der Versorgungseinheit 4 untergebracht sind.
Bei dieser Ausführungsform der Vorrichtung 1a ergibt sich eine
kompakte Einheit, die innerhalb des Körpers über einen entsprechenden
Behandlungszeitraum als autarke Einheit verbleiben
kann.
Die Unterseitenansicht gemäß Figur 5 zeigt noch im Bereich der
Auflage- und Kontaktfläche 13, innerhalb der sich auch die poröse
Membrane 9 sowie der oder die Sensoren 10 befinden, in den
Eckbereichen beziehungsweise randseitig angeordnete Haftregionen
14. Mittels dieser Haftregionen 14 kann der Sensor-Aktuatorkopf
3a beziehungsweise auch der Sensor-Aktuatorkopf 3 gemäß Figur
1 und 2 an den zu behandelnden Bereich angedrückt werden und wird
dann durch adhäsives Anhaften gehalten.
Die Haftregionen 14 können auch für iontophoretische Zwecke
verwendet werden und sind dann elektrisch leitend ausgebildet
und über Anschlußleitungen mit einer Spannungsquelle verbunden.
Als Stromversorgung für die Dosiersteuerung und dergleichen kann
eine auswechselbare oder aufladbare Batterie 8 (Figur 1) vorgesehen
sein oder aber es besteht auch die Möglichkeit, daß eine
thermoelektrische oder eine unter Zuhilfenahme der Körperflüssigkeit
gebildete, galvanische Stromversorgung vorgesehen ist.
Thermoelektrische oder galvanische Stromversorgungen sind
insbesondere in Verbindung mit der in Figur 4 und 5 gezeigten
Ausführungsform der erfindungsgemäßen Vorrichtung vorteilhaft. Ion-selective field effect transistors (IS-FET) are preferably used as the pH sensor.
In addition,
Figures 4 and 5 show a modified embodiment of a
In this embodiment of the
The underside view according to FIG. 5 still shows in the area of the support and
The
Figur 6 zeigt noch eine weitere Ausführungsvariante eines Sensor-Aktuatorkopfes
3b, der im wesentlichen röhrenförmig ausgebildet
ist und an seiner äußeren Mantelfläche eine streifenförmig
längsorientierte Auflage- und Kontaktfläche aufweist. Diese
Ausführungsform kommt insbesondere zur Behandlung innerhalb von
Hohlorganen zur Anwendung. Erwähnt sei hierbei, daß auch mehrere
Auflage- und Kontaktflächen am Umfang des röhrenförmigen Sensor-Aktuatorkopfes
verteilt vorgesehen sein können. Auch die anderen
Ausführungsformen von Applikationsköpfen können mit mehreren
Auflage- und Kontaktflächen und innerhalb von diesen befindlichen
porösen Membranen 9 und Sensoren 10 ausgerüstet sein.
An einem Ende des röhrenförmigen Sensor-Aktuatorkopfes 3b ist
noch ein Anschluß 15 für einen externen Wirkstoffbehälter,
insbesondere zum Nachfüllen von Wirkstoff angedeutet.FIG. 6 shows yet another embodiment variant of a sensor / actuator head 3b, which is essentially tubular and has a strip-shaped, longitudinally oriented support and contact surface on its outer surface. This embodiment is used in particular for treatment within hollow organs. It should be mentioned here that several support and contact surfaces can also be provided distributed around the circumference of the tubular sensor actuator head. The other embodiments of application heads can also be equipped with a plurality of support and contact surfaces and within them
At one end of the tubular sensor-actuator head 3b, a
Claims (14)
- A device for treating living cell tissue, where the device comprises a sensor actuator head (3, 3a, 3b) having a pH sensor and a drug dispensing device having a reservoir (6) storing the drug, and where the pH sensor and the drug dispensing device are connected to a control device for dosing the drug as a function of the pH value measurement,
characterised in that the sensor actuator head (3, 3a, 3b) at least with the pH sensor (10) and the drug dispensing device is constructed in such a manner that it can be inserted inside the body in the tumorous tissue region and in the application position in this contacts this treatment area with a supporting and contact surface (13),
in that the pH sensor (10) is provided to determine the acidulation of the direct vicinity of this tumorous tissue region,
and in that the drug is one intended for the variation of the pH value in the direct vicinity of the tumorous tissue region and/or for the reduction of the acidulation of the tumour cells. - A device especially according to Claim 1,
characterised in that at the sensor actuator head electrodes are provided for physically influencing the tumorous tissue region by electrical and/or electromagnetic fields by means of iontophoresis to raise the measured pH value in the direct vicinity of a tumorous tissue region. - A device according to Claim 1,
characterised in that the drug dispensing device preferably comprises at least one porous membrane (9) forming the supporting and contact surface and a drug supply to this membrane
and in that during the supply of drug a dosing device is provided, which is connected to a dosage control device (7). - A device according to Claim 3,
characterised in that the sensor or sensors (10) are disposed adjacent to the membrane (9). - A device according to one of Claims 1 to 4,
characterised in that for the supporting and contract surface (13) for the tissue area to be treated, at least two electrodes, which are connected via electric lines to a voltage source, are provided for iontophoretic purposes. - A device according to one of Claims 1 to 5,
characterised in that for the supporting and contact surface (13) of the sensor actuator head (3, 3a, 3b), adhesive regions (14) are provided, in particular at the edge, for the preferably adhesive bonding of the sensor actuator head to the tissue area (2) to be treated
and in that the adhesive regions (14) of the sensor actuator head possibly have an electrically conductive construction and at the same time serve as an electrode for the iontophoresis. - A device according to one of Claims 1 to 6,
characterised in that the pH sensor is constructed on a semiconductor base or on the base/basis of a conductivity and impedance measurement
and in that in the case of a pH sensor on a semiconductor base at least one ion-selective field-effect transistor is preferably provided for this. - A device according to one of Claims 1 to 7,
characterised in that in addition to at least one pH sensor, at least one further sensor is provided, in particular an ion or molecular sensor. - A device according to one of Claims 3 to 8,
characterised in that the sensor actuator head (la) forms a complete functional unit
and in that this comprises in particular at least one reservoir (6) for the drug, one or more dosing device(s) with dosage control device (7) connected to the porous membrane (9) or the like and also at least one pH sensor (10). - A device according to Claim 8,
characterised in that the sensor actuator head constructed as a functional unit comprises at least one pH sensor(10), at least two electrodes for iontophoretic purposes, a voltage source and also a control device. - A device according to one of Claims 1 to 10,
characterised in that the sensor actuator head (3b) has a substantially tubular construction and, in particular on its shell surface, comprises at least one supporting and contact surface (13) which is longitudinally orientated like a strip for the tissue area to be treated. - A device according to one of Claims 1 to 8 or 11,
characterised in that the reservoir (6) for the drug, preferably together with the dosing device and the dosage control device (7), is disposed removed from the sensor actuator head (3)
and in that one or more connecting lines (5) is provided between these functional groups, in particular to supply the drug in doses to the sensor actuator head (3) and/or for connection with the electrodes. - A device according to one of Claims 1 to 12,
characterised in that a connection (15) for an external drug reservoir, in particularly for topping up the drug, is provided at the sensor actuator head (3b). - A device according to one of Claims 1 to 13,
characterised in that a battery situated in the sensor actuator head or in a functional unit removed therefrom and/or a thermoelectric and/or a galvanic current supply, which is formed with the aid of body fluid, is provided as the current supply for the device.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19601487 | 1996-01-17 | ||
| DE19601487A DE19601487C2 (en) | 1996-01-17 | 1996-01-17 | Device for treating malignant tissue changes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| EP0784992A2 EP0784992A2 (en) | 1997-07-23 |
| EP0784992A3 EP0784992A3 (en) | 1997-11-19 |
| EP0784992B1 true EP0784992B1 (en) | 2003-04-09 |
Family
ID=7782958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP97100159A Expired - Lifetime EP0784992B1 (en) | 1996-01-17 | 1997-01-08 | Treatment device for malignant changes of tissue |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US5820548A (en) |
| EP (1) | EP0784992B1 (en) |
| JP (1) | JP3957800B2 (en) |
| DE (2) | DE19601487C2 (en) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19717023C2 (en) | 1997-04-23 | 2003-02-06 | Micronas Gmbh | Device for treating malignant, tumorous tissue areas |
| JPH1154632A (en) * | 1997-08-01 | 1999-02-26 | Mitsubishi Electric Corp | Layout pattern for memory cell |
| US6738663B2 (en) | 1999-04-09 | 2004-05-18 | Oncostim, A Minnesota Corporation | Implantable device and method for the electrical treatment of cancer |
| US6366808B1 (en) | 2000-03-13 | 2002-04-02 | Edward A. Schroeppel | Implantable device and method for the electrical treatment of cancer |
| US8024048B2 (en) * | 2000-03-13 | 2011-09-20 | Ionix Medical Inc. | Method and device for treating cancer with electrical therapy in conjunction with chemotherapeutic agents and radiation therapy |
| US7742811B2 (en) * | 2000-03-13 | 2010-06-22 | Onco Stim | Implantable device and method for the electrical treatment of cancer |
| DE20113761U1 (en) * | 2001-08-20 | 2001-12-20 | Lohmann & Rauscher GmbH & Co. KG, 56567 Neuwied | Wound Care Product |
| AU2003299471A1 (en) | 2002-05-07 | 2004-05-13 | Kai Kroll | Method and device for treating concer with electrical therapy in conjunction with chemotherapeutic agents and radiation therapy |
| US7079890B2 (en) * | 2003-03-19 | 2006-07-18 | Solco Biomedical Co., Ltd. | Electrochemical therapy apparatus |
| DK1662987T3 (en) * | 2003-09-11 | 2012-02-27 | Theranos Inc | Medical device for analyte monitoring and drug delivery |
| US7720549B2 (en) * | 2004-04-06 | 2010-05-18 | Oncostim, Inc. | Partially implantable system for the electrical treatment of abnormal tissue growth |
| US20050222646A1 (en) * | 2004-04-06 | 2005-10-06 | Kai Kroll | Method and device for treating cancer with modified output electrical therapy |
| US7155269B2 (en) * | 2005-03-11 | 2006-12-26 | Tanita Corporation | Stress evaluation apparatus |
| CA2610294C (en) | 2005-05-09 | 2023-10-03 | Theranos, Inc. | Point-of-care fluidic systems and uses thereof |
| US8741230B2 (en) | 2006-03-24 | 2014-06-03 | Theranos, Inc. | Systems and methods of sample processing and fluid control in a fluidic system |
| US11287421B2 (en) | 2006-03-24 | 2022-03-29 | Labrador Diagnostics Llc | Systems and methods of sample processing and fluid control in a fluidic system |
| US8007999B2 (en) | 2006-05-10 | 2011-08-30 | Theranos, Inc. | Real-time detection of influenza virus |
| US20080113391A1 (en) | 2006-11-14 | 2008-05-15 | Ian Gibbons | Detection and quantification of analytes in bodily fluids |
| US8158430B1 (en) | 2007-08-06 | 2012-04-17 | Theranos, Inc. | Systems and methods of fluidic sample processing |
| DE102008021575A1 (en) | 2008-04-30 | 2009-11-05 | Neue Magnetodyn Gmbh | Device for stimulating a healing process |
| US9597145B2 (en) | 2008-08-20 | 2017-03-21 | Prostacare Pty Ltd | Non-thermal ablation system for treating tissue |
| NZ624935A (en) | 2009-10-19 | 2016-01-29 | Theranos Inc | Integrated health data capture and analysis system |
| CN107080867B (en) * | 2017-05-27 | 2019-10-11 | 李福宝 | A kind of Internal Medicine-Oncology drug interventional therapy device |
| DE202018106744U1 (en) | 2017-11-27 | 2019-05-13 | Prostacare Pty Ltd | Device for the treatment of a prostate disease |
| US11224474B2 (en) | 2018-02-28 | 2022-01-18 | Prostacare Pty Ltd | System for managing high impedance changes in a non-thermal ablation system for BPH |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4003379A (en) * | 1974-04-23 | 1977-01-18 | Ellinwood Jr Everett H | Apparatus and method for implanted self-powered medication dispensing |
| US4402694A (en) * | 1981-07-16 | 1983-09-06 | Biotek, Inc. | Body cavity access device containing a hormone source |
| DE3321831A1 (en) * | 1983-06-15 | 1983-11-24 | Armin 1000 Berlin Pohlenz | Double-chamber electrolysis device for influencing cellular tissues, especially those of tumours |
| US5135479A (en) * | 1983-08-18 | 1992-08-04 | Drug Delivery Systems, Inc. | Programmable control and mounting system for transdermal drug applicator |
| US4800899A (en) * | 1984-10-22 | 1989-01-31 | Microthermia Technology, Inc. | Apparatus for destroying cells in tumors and the like |
| DE3601730A1 (en) * | 1985-01-23 | 1986-09-11 | Horst 2000 Hamburg Mau | Method and device for identifying and controlling body fluid values |
| SE455920B (en) * | 1986-01-29 | 1988-08-22 | Hans Wiksell | TUMOR HYPERTERMY TREATMENT DEVICE |
| US4784158A (en) * | 1987-08-21 | 1988-11-15 | Okimoto Paul M | Vaginal testing applicator and method |
| US5413915A (en) * | 1988-07-12 | 1995-05-09 | Resource Technologies Group, Inc. | Method and sensor for detecting toxic chemical exposure effects and metabolic activation of carcinogenic chemical agents |
| HRP921157A2 (en) * | 1991-12-20 | 1994-10-31 | Lohmann Therapie Syst Lts | Transdermal system of applying acetilsalicilyc acid in antithrombosys therapy |
| CA2153993A1 (en) * | 1992-01-16 | 1993-08-05 | Rakesh K. Jain | Method and apparatus for locating tumors |
| US5301688A (en) * | 1992-08-07 | 1994-04-12 | Physion S.R.L. | Method for localization and therapy of occult bladder cancer |
| JPH07500523A (en) * | 1992-08-28 | 1995-01-19 | コートラック・メディカル・インコーポレーテッド | Polymer matrix drug delivery device and method |
| US5421816A (en) * | 1992-10-14 | 1995-06-06 | Endodermic Medical Technologies Company | Ultrasonic transdermal drug delivery system |
| DE4300018A1 (en) * | 1993-01-02 | 1995-03-23 | Knedla Richard Dr | Method and the technical solution for carrying out the medical electrotherapy which can preferably be applied in the treatment of diseases, such as various forms of cancer, leukaemia, neurofibromatosis, AIDS and various forms of tropical viral diseases, etc. |
-
1996
- 1996-01-17 DE DE19601487A patent/DE19601487C2/en not_active Expired - Fee Related
-
1997
- 1997-01-08 DE DE59709729T patent/DE59709729D1/en not_active Expired - Fee Related
- 1997-01-08 EP EP97100159A patent/EP0784992B1/en not_active Expired - Lifetime
- 1997-01-13 JP JP00362797A patent/JP3957800B2/en not_active Expired - Fee Related
- 1997-01-15 US US08/784,845 patent/US5820548A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE19601487C2 (en) | 2001-09-13 |
| EP0784992A2 (en) | 1997-07-23 |
| JP3957800B2 (en) | 2007-08-15 |
| JPH10179763A (en) | 1998-07-07 |
| US5820548A (en) | 1998-10-13 |
| EP0784992A3 (en) | 1997-11-19 |
| DE59709729D1 (en) | 2003-05-15 |
| DE19601487A1 (en) | 1997-07-24 |
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